Clinical intuition suggests that personality disorders hinder the treatment of depression, but research findings are mixed. One reason for this might be the way in which current assessment measures conflate general aspects of personality disorders, such as overall severity, with specific aspects, such as stylistic tendencies. The goal of this study was to clarify the unique contributions of the general and specific aspects of personality disorders to depression outcomes.

Patients admitted to the Menninger Clinic, Houston, between 2012 and 2015 (N = 2352) were followed over a 6–8-week course of multimodal inpatient treatment. Personality disorder symptoms were assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition Axis II Personality Screening Questionnaire at admission, and depression severity was assessed using the Patient Health Questionnaire-9 every fortnight. General and specific personality disorder factors estimated with a confirmatory bifactor model were used to predict latent growth curves of depression scores in a structural equation model.

The general factor predicted higher initial depression scores but not different rates of change. By contrast, the specific borderline factor predicted slower rates of decline in depression scores, while the specific antisocial factor predicted a U shaped pattern of change.

Personality disorder symptoms are best represented by a general factor that reflects overall personality disorder severity, and specific factors that reflect unique personality styles. The general factor predicts overall depression severity while specific factors predict poorer prognosis which may be masked in prior studies that do not separate the two.

Maternal smoking has known adverse effects on fetal development. However, research on the association between maternal smoking during pregnancy and offspring intellectual disability (ID) is limited, and whether any associations are due to a causal effect or residual confounding is unknown.

Cohort study of all Danish births between 1995 and 2012 (1 066 989 persons from 658 335 families after exclusions), with prospectively recorded data for cohort members, parents and siblings. We assessed the association between maternal smoking during pregnancy (18.6% exposed, collected during prenatal visits) and offspring ID (8051 cases, measured using ICD-10 diagnosis codes F70–F79) using logistic generalised estimating equation regression models. Models were adjusted for confounders including measures of socio-economic status and parental psychiatric diagnoses and were adjusted for family averaged exposure between full siblings. Adjustment for a family averaged exposure allows calculation of the within-family effect of smoking on child outcomes which is robust against confounders that are shared between siblings.

We found increased odds of ID among those exposed to maternal smoking in pregnancy after confounder adjustment (OR 1.35, 95% CI 1.28–1.42) which attenuated to a null effect following adjustment for family averaged exposure (OR 0.91, 95% CI 0.78–1.06).

Our findings are inconsistent with a causal effect of maternal smoking during pregnancy on offspring ID risk. By estimating a within-family effect, our results suggest that prior associations were the result of unmeasured genetic or environmental characteristics of families in which the mother smokes during pregnancy.

Individuals exhibiting gender nonconforming behaviors experience low self-esteem and a number of other mental health conditions, including elevated suicide risk. Most of the relevant evidence is confined to US studies, however. Adopting a cross-national approach, we examined the pervasiveness of the psychological burden associated with gender nonconformity. Because self-esteem is sensitive to the fulfillment of societal expectations for gender conformity, we reasoned that the relationship between gender conformity and self-esteem ought to decrease as societies become less restrictive in their gender norms.

To test this proposition, we conducted two studies including 18 national samples from 15 countries varying in gender equality. Participants responded to an online survey that included measures of gender conformity and self-esteem (N = 4486).

Using multilevel analyses and meta-analytic statistics over the samples of both studies, we found that as gender equality increased, the association between gender conformity and self-esteem decreased.

The results suggest that rather than being inherently noxious, gender non-conformity becomes detrimental to self-esteem when it clashes with restrictive gender role norms that are enacted by the macrosocial context. We suggest that previous findings on psychological problems related to gender nonconformity be considered within a broader macrosocial context that may constrain people's freedom to move against gender role norms.

A possible role of vitamin D in the pathophysiology of depression is currently speculative, with more rigorous research needed to assess this association in large adult populations. The current study assesses prospective associations between vitamin D status and depression in middle-aged adults enrolled in the UK Biobank.

We assessed prospective associations between vitamin D status at the baseline assessment (2006–2010) and depression measured at the follow-up assessment (2016) in 139 128 adults registered with the UK Biobank.

Amongst participants with no depression at baseline (n = 127 244), logistic regression revealed that those with vitamin D insufficiency [adjusted odds ratio (aOR) = 1.14, 95% confidence interval (CI) = 1.07–1.22] and those with vitamin D deficiency (aOR = 1.24, 95% CI 1.13–1.36) were more likely to develop new-onset depression at follow-up compared with those with optimal vitamin D levels after adjustment for a wide range of relevant covariates. Similar prospective associations were reported for those with depression at baseline (n = 11 884) (insufficiency: aOR = 1.11, 95% CI 1.00–1.23; deficiency: aOR = 1.30, 95% CI 1.13–1.50).

The prospective associations found between vitamin D status and depression suggest that both vitamin D deficiency and insufficiency might be risk factors for the development of new-onset depression in middle-aged adults. Moreover, vitamin D deficiency (and to a lesser extent insufficiency) might be a predictor of sustained depressive symptoms in those who are already depressed. Vitamin D deficiency and insufficiency is very common, meaning that these findings have significant implications for public health.

The Patient Health Questionnaire (PHQ-9), the Beck Depression Inventory (BDI-II) and the Generalised Anxiety Disorder Assessment (GAD-7) are widely used in the evaluation of interventions for depression and anxiety. The smallest reduction in depressive symptoms that matter to patients is known as the Minimum Clinically Important Difference (MCID). Little empirical study of the MCID for these scales exists.

A prospective cohort of 400 patients in UK primary care were interviewed on four occasions, 2 weeks apart. At each time point, participants completed all three questionnaires and a ‘global rating of change’ scale (GRS). MCID estimation relied on estimated changes in symptoms according to reported improvement on the GRS scale, stratified by baseline severity on the Clinical Interview Schedule (CIS-R).

For moderate baseline severity, those who reported improvement on the GRS had a reduction of 21% (95% confidence interval (CI) −26.7 to −14.9) on the PHQ-9; 23% (95% CI −27.8 to −18.0) on the BDI-II and 26.8% (95% CI −33.5 to −20.1) on the GAD-7. The corresponding threshold scores below which participants were more likely to report improvement were −1.7, −3.5 and −1.5 points on the PHQ-9, BDI-II and GAD-7, respectively. Patients with milder symptoms require much larger reductions as percentage of their baseline to endorse improvement.

An MCID representing 20% reduction of scores in these scales, is a useful guide for patients with moderately severe symptoms. If treatment had the same effect on patients irrespective of baseline severity, those with low symptoms are unlikely to notice a benefit.

Funding. National Institute for Health Research.

Childhood exposure to interpersonal violence (IPV) may be linked to distinct manifestations of mental illness, yet the nature of this change remains poorly understood. Network analysis can provide unique insights by contrasting the interrelatedness of symptoms underlying psychopathology across exposed and non-exposed youth, with potential clinical implications for a treatment-resistant population. We anticipated marked differences in symptom associations among IPV-exposed youth, particularly in terms of ‘hub’ symptoms holding outsized influence over the network, as well as formation and influence of communities of highly interconnected symptoms.

Participants from a population-representative sample of youth (n = 4433; ages 11–18 years) completed a comprehensive structured clinical interview assessing mental health symptoms, diagnostic status, and history of violence exposure. Network analytic methods were used to model the pattern of associations between symptoms, quantify differences across diagnosed youth with (IPV+) and without (IPV–) IPV exposure, and identify transdiagnostic ‘bridge’ symptoms linking multiple disorders.

Symptoms organized into six ‘disorder’ communities (e.g. Intrusive Thoughts/Sensations, Depression, Anxiety), that exhibited considerably greater interconnectivity in IPV+ youth. Five symptoms emerged in IPV+ youth as highly trafficked ‘bridges’ between symptom communities (11 in IPV– youth).

IPV exposure may alter mutually reinforcing symptom co-occurrence in youth, thus contributing to greater psychiatric comorbidity and treatment resistance. The presence of a condensed and unique set of bridge symptoms suggests trauma-enriched nodes which could be therapeutically targeted to improve outcomes in violence-exposed youth.

Sibling resemblance in crime may be due to genetic relatedness, shared environment, and/or the interpersonal influence of siblings on each other. This latter process can be understood as a type of ‘peer effect’ in that it is based on social learning between individuals occupying the same status in the social system (family). Building on prior research, we hypothesized that sibling pairs that resemble peer relationships the most, i.e., same-sex siblings close in age, exhibit the most sibling resemblance in crime.

Drawing on administrative microdata covering Finnish children born in 1985–97, we examined 213 911 sibling pairs, observing the recorded criminality of each sibling between ages 11 and 20. We estimated multivariate regression models controlling for individual and family characteristics, and employed fixed-effects models to analyze the temporal co-occurrence of sibling delinquency.

Among younger siblings with a criminal older sibling, the adjusted prevalence estimates of criminal offending decreased from 32 to 25% as the age differences increased from less than 13 months to 25–28 months. The prevalence leveled off at 23% when age difference reached 37–40 months or more. These effects were statistically significant only among same-sex sibling pairs (p < 0.001), with clear evidence of contemporaneous offending among siblings with minimal age difference.

Same-sex siblings very close in age stand out as having the highest sibling resemblance in crime. This finding suggests that a meaningful share of sibling similarity in criminal offending is due to a process akin to peer influence, typically flowing from the older to the younger sibling.

Suicide and cardiovascular disease rank among the leading causes of disability and premature mortality worldwide. Young adult suicide attempters are at increased risk of mortality from cardiovascular disease even compared to those with major depressive disorder suggesting an increased burden of cardiovascular risk factors. We compared the cardiovascular risk burden between youth attempters and other high-risk individuals.

Participants were from the Collaborative Psychiatric Epidemiology Surveys (CPES), a U.S. population-based study, aged 18–30 years [suicide attempt (SA): n = 303; suicidal ideation (SI): n = 451; controls: n = 3671]; and psychiatric inpatients admitted for a SA (n = 38) or SI (n = 40) and healthy controls (n = 37) aged 15–30 years. We computed a cardiovascular risk score and high- and low-risk latent classes based on risk factors of high blood pressure, obesity, and smoking.

Suicide attempters showed an increased cardiovascular risk score (CPES: B = 0.43, 95% confidence interval (CI) 0.31–0.54, p < 0.001; inpatient sample: B = 1.61, 95% CI 0.53–2.68, p = 0.004) compared to controls. They were also more likely to be classified in the high cardiovascular risk group (CPES: odds ratio (OR) 3.36, 95% CI 1.67–6.78, p = 0.001; inpatient sample: OR 9.89, 95% CI 1.38–85.39, p = 0.03) compared to those with SI (CPES: OR 1.15, 95% CI 0.55–2.39, p = 0.71; inpatient sample: OR 1.91, 95% CI 0.25–15.00, p = 0.53).

Youth attempters show an increased burden for cardiovascular risk compared to other high-risk individuals in inpatient and population-based samples. Clinicians should pay particular attention to cardiovascular risk factors among suicide attempters in order to reduce their risk for cardiovascular events.

There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation.

We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls.

The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: −0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465).

The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

The Syrian crisis has entered its ninth year with many being affected by the war. This is the largest-scale study that aims to evaluate the psychological profile of secondary school students in Syria.

This is a cross-sectional study in schools in Damascus, Syria. The surveys assessed working habits, smoking, war exposure, grades, socioeconomic status (SES), social support, health-related quality of life (HRQL), post-traumatic stress disorder (PTSD), problematic anger, and other parameters.

This study included 1369 students of which 53% suffered from PTSD and 62% from problematic anger. Around 46% declared a fair or worse general health and 61% had moderate or severe mental health. Only 9.3% did not report exposure to any war-related variable. War exposure had an impact on PTSD, anger, and HRQL, but not on students' grades. Smoking, having consanguineous parents, and working did not have a clear association with grades or anger. Social support weakly reduced PTSD and anger scores. Interestingly, working was associatedwith lowerPTSD scores but was associated with a worse physical component of HRQL.

This is the largest study on school students in Syria that reports the psychological ramifications of war. Although the direct effects of war could not be precisely described, the high burden of PTSD and anger distress was a strong reflection of the chronic mental distress.

This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.

We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.

Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.

These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.

Major depressive disorder (MDD) is a leading cause of morbidity and mortality. Shortfalls in treatment quantity and quality are well-established, but the specific gaps in pharmacotherapy and psychotherapy are poorly understood. This paper analyzes the gap in treatment coverage for MDD and identifies critical bottlenecks.

Seventeen surveys were conducted across 15 countries by the World Health Organization-World Mental Health Surveys Initiative. Of 35 012 respondents, 3341 met DSM-IV criteria for 12-month MDD. The following components of effective treatment coverage were analyzed: (a) any mental health service utilization; (b) adequate pharmacotherapy; (c) adequate psychotherapy; and (d) adequate severity-specific combination of both.

MDD prevalence was 4.8% (s.e., 0.2). A total of 41.8% (s.e., 1.1) received any mental health services, 23.2% (s.e., 1.5) of which was deemed effective. This 90% gap in effective treatment is due to lack of utilization (58%) and inadequate quality or adherence (32%). Critical bottlenecks are underutilization of psychotherapy (26 percentage-points reduction in coverage), underutilization of psychopharmacology (13-point reduction), inadequate physician monitoring (13-point reduction), and inadequate drug-type (10-point reduction). High-income countries double low-income countries in any mental health service utilization, adequate pharmacotherapy, adequate psychotherapy, and adequate combination of both. Severe cases are more likely than mild-moderate cases to receive either adequate pharmacotherapy or psychotherapy, but less likely to receive an adequate combination.

Decision-makers need to increase the utilization and quality of pharmacotherapy and psychotherapy. Innovations such as telehealth for training and supervision plus non-specialist or community resources to deliver pharmacotherapy and psychotherapy could address these bottlenecks.

The neuropeptide oxytocin is proposed as a promising therapy for social dysfunction by modulating amygdala-mediated social-emotional behavior. Although clinical trials report some benefits of chronic treatment, it is unclear whether efficacy may be influenced by dose frequency or genotype.

In a randomized, double-blind, placebo-controlled pharmaco-functional magnetic resonance imaging trial (150 male subjects), we investigated acute and different chronic (every day or on alternate days for 5 days) intranasal oxytocin (24 international units) effects and oxytocin receptor genotype-mediated treatment sensitivity on amygdala responses to face emotions. We also investigated similar effects on resting-state functional connectivity between the amygdala and prefrontal cortex.

A single dose of oxytocin-reduced amygdala responses to all face emotions but for threatening (fear and anger) and happy faces, this effect was abolished after daily doses for 5 days but maintained by doses given every other day. The latter dose regime also enhanced associated anxious-arousal attenuation for fear faces. Oxytocin effects on reducing amygdala responses to face emotions only occurred in AA homozygotes of rs53576 and A carriers of rs2254298. The effects of oxytocin on resting-state functional connectivity were not influenced by either dose-frequency or receptor genotype.

Infrequent chronic oxytocin administration may be therapeutically most efficient and its anxiolytic neural and behavioral actions are highly genotype-dependent in males.

A hospital built environment can affect patients’ treatment satisfaction, which is, in turn, associated with crucial clinical outcomes. However, little research has explored which elements are specifically important for psychiatric in-patients. This study aims to identify which elements of the hospital environment are associated with higher patient satisfaction with psychiatric in-patient care.

The study was conducted in Italy and the United Kingdom. Data was collected through hospital visits and patient interviews. All hospitals were assessed for general characteristics, aspects specific to psychiatry (patient safety, mixed/single-sex wards, smoking on/off wards), and quality of hospital environment. Patients’ treatment satisfaction was assessed using the Client Assessment of Treatment Scale (CAT). Multi-level modelling was used to explore the role of environment in predicting the CAT scores adjusted for age, gender, education, diagnosis, and formal status.

The study included 18 psychiatric hospitals (7 in Italy and 11 in the United Kingdom) and 2130 patients. Healthcare systems in these countries share key characteristics (e.g. National Health Service, care organised on a geographical basis) and differ in policy regulation and governance. Two elements were associated with higher patient treatment satisfaction: being hospitalised on a mixed-sex ward (p = 0.003) and the availability of rooms to meet family off wards (p = 0.020).

As hospitals are among the most expensive facilities to build, their design should be guided by research evidence. Two design features can potentially improve patient satisfaction: family rooms off wards and mixed-sex wards. This evidence should be considered when designing or renovating psychiatric facilities.

Genetics hold promise of predicting long-term post-traumatic stress disorder (PTSD) outcomes following trauma. The aim of the current study was to test whether six hypothesized polygenic risk scores (PRSs) developed to capture genetic vulnerability to psychiatric conditions prospectively predict PTSD onset, severity, and 18-year course after trauma exposure.

Participants were 1490 responders to the World Trade Center (WTC) disaster (mean age at 9/11 = 38.81 years, s.d. = 8.20; 93.5% male; 23.8% lifetime WTC-related PTSD diagnosis). Prospective longitudinal data on WTC-related PTSD symptoms were obtained from electronic medical records and modelled as PTSD trajectories using growth mixture model analysis. Independent regression models tested whether six hypothesized psychiatric PRSs (PTSD-PRS, Re-experiencing-PRS, Generalized Anxiety-PRS, Schizophrenia-PRS, Depression-PRS, and Neuroticism-PRS) are predictive of WTC-PTSD outcomes: lifetime diagnoses, average symptom severity, and 18-year symptom trajectory. All analyses were adjusted for population stratification, 9/11 exposure severity, and multiple testing.

Depression-PRS predicted PTSD diagnostic status (OR 1.37, CI 1.17–1.61, adjusted p = 0.001). All PRSs, except PTSD-PRS, significantly predicted average PTSD symptoms (β = 0.06–0.10, adjusted p < 0.05). Re-experiencing-PRS, Generalized Anxiety-PRS and Schizophrenia-PRS predicted the high severity PTSD trajectory class (ORs 1.21–1.28, adjusted p < 0.05). Finally, PRSs prediction was independent of 9/11 exposure severity and jointly accounted for 3.7 times more variance in PTSD symptoms than the exposure severity.

Psychiatric PRSs prospectively predicted WTC-related PTSD lifetime diagnosis, average symptom severity, and 18-year trajectory in responders to 9/11 disaster. Jointly, PRSs were more predictive of subsequent PTSD than the exposure severity. In the future, PRSs may help identify at-risk responders who might benefit from targeted prevention approaches.

Predictors of new-onset bipolar disorder (BD) or psychotic disorder (PD) have been proposed on the basis of retrospective or prospective studies of ‘at-risk’ cohorts. Few studies have compared concurrently or longitudinally factors associated with the onset of BD or PDs in youth presenting to early intervention services. We aimed to identify clinical predictors of the onset of full-threshold (FT) BD or PD in this population.

Multi-state Markov modelling was used to assess the relationships between baseline characteristics and the likelihood of the onset of FT BD or PD in youth (aged 12–30) presenting to mental health services.

Of 2330 individuals assessed longitudinally, 4.3% (n = 100) met criteria for new-onset FT BD and 2.2% (n = 51) met criteria for a new-onset FT PD. The emergence of FT BD was associated with older age, lower social and occupational functioning, mania-like experiences (MLE), suicide attempts, reduced incidence of physical illness, childhood-onset depression, and childhood-onset anxiety. The emergence of a PD was associated with older age, male sex, psychosis-like experiences (PLE), suicide attempts, stimulant use, and childhood-onset depression.

Identifying risk factors for the onset of either BD or PDs in young people presenting to early intervention services is assisted not only by the increased focus on MLE and PLE, but also by recognising the predictive significance of poorer social function, childhood-onset anxiety and mood disorders, and suicide attempts prior to the time of entry to services. Secondary prevention may be enhanced by greater attention to those risk factors that are modifiable or shared by both illness trajectories.